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      Association between small for gestational age and risk of autism spectrum disorders: a meta-analysis

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          Abstract

          Background

          The relationship between small for gestational age (SGA) and autism spectrum disorders (ASDs) remains unknown.

          Purpose

          This meta-analysis aimed to investigate the relationship between SGA and the risk of ASD.

          Methods

          We searched PubMed, Web of Science, and Scopus databases from inception to November 2020. The heterogeneity across studies was explored using the I 2 statistic. The possibility of publication bias was assessed using Begg test. The results were reported using the odds ratio (OR) and 95% confidence interval (CI) using a random-effects model.

          Results

          The literature search yielded 824 articles with 8,752,138 participants. We assessed the association between SGA and the risk of ASD in cohort and case-control studies. Based on the random-effects model, compared with SGA, the estimated OR of the risk of ASD was 1.17 (95% CI, 1.09–1.24). Therefore, there was a significant association between SGA and the risk of ASD.

          Conclusion

          Based on OR reports in epidemiological studies, we showed that SGA is a risk factor for and can increase the risk of ASD. The association between SGA and ASD risk has further relevance to the current public health emphasis on appropriate prepregnancy weight and pregnancy weight gain.

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          Most cited references31

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          Measuring inconsistency in meta-analyses.

          Julian P. T. Higgins, Simon Thompson, Jonathan Deeks … (2003)
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            Bias in meta-analysis detected by a simple, graphical test.

            M. Egger, G Davey Smith, M. Schneider … (1997)
            Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews. Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.
            Article 0 comments Cited 1601 times – based on 0 reviews     Review now
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              Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses

              Amirhossein Modabbernia, Eva Velthorst, Abraham Reichenberg (2017)
              Background According to recent evidence, up to 40–50% of variance in autism spectrum disorder (ASD) liability might be determined by environmental factors. In the present paper, we conducted a review of systematic reviews and meta-analyses of environmental risk factors for ASD. We assessed each review for quality of evidence and provided a brief overview of putative mechanisms of environmental risk factors for ASD. Findings Current evidence suggests that several environmental factors including vaccination, maternal smoking, thimerosal exposure, and most likely assisted reproductive technologies are unrelated to risk of ASD. On the contrary, advanced parental age is associated with higher risk of ASD. Birth complications that are associated with trauma or ischemia and hypoxia have also shown strong links to ASD, whereas other pregnancy-related factors such as maternal obesity, maternal diabetes, and caesarian section have shown a less strong (but significant) association with risk of ASD. The reviews on nutritional elements have been inconclusive about the detrimental effects of deficiency in folic acid and omega 3, but vitamin D seems to be deficient in patients with ASD. The studies on toxic elements have been largely limited by their design, but there is enough evidence for the association between some heavy metals (most important inorganic mercury and lead) and ASD that warrants further investigation. Mechanisms of the association between environmental factors and ASD are debated but might include non-causative association (including confounding), gene-related effect, oxidative stress, inflammation, hypoxia/ischemia, endocrine disruption, neurotransmitter alterations, and interference with signaling pathways. Conclusions Compared to genetic studies of ASD, studies of environmental risk factors are in their infancy and have significant methodological limitations. Future studies of ASD risk factors would benefit from a developmental psychopathology approach, prospective design, precise exposure measurement, reliable timing of exposure in relation to critical developmental periods and should take into account the dynamic interplay between gene and environment by using genetically informed designs. Electronic supplementary material The online version of this article (doi:10.1186/s13229-017-0121-4) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Exp Pediatr
                Journal ID (iso-abbrev): Clin Exp Pediatr
                Journal ID (publisher-id): CEP
                Title: Clinical and Experimental Pediatrics
                Publisher: Korean Pediatric Society
                ISSN (Electronic): 2713-4148
                Publication date Collection: October 2021
                Publication date (Electronic): 28 January 2021
                Volume: 64
                Issue: 10
                Pages: 538-542
                Affiliations
                [1 ]Autism Spectrum Disorders Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
                [2 ]Social Determinants of Health Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
                [3 ]Department of Midwifery, Tuyserkan Branch, Islamic Azad University, Tuyserkan, Iran
                Author notes
                Corresponding author: Mahdieh Seyedi, MSc. Autism Spectrum Disorders Research Center, Hamadan University of Medical Sciences, Fahmideh Street, Hamadan, Iran Email: mahdiehseyedi@ 123456gmail.com
                Author information
                http://orcid.org/0000-0002-4536-0814
                http://orcid.org/0000-0003-2133-087X
                http://orcid.org/0000-0002-8127-5000
                http://orcid.org/0000-0001-7149-6216
                Article
                Publisher ID: cep-2020-01956
                DOI: 10.3345/cep.2020.01956
                PMC ID: 8498018
                PubMed ID: 33539699
                SO-VID: 0798446a-4b0f-422b-b80f-b83f24738b04
                Copyright © Copyright © 2021 by The Korean Pediatric Society
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 3 December 2020
                Date revision received : 13 January 2021
                Date accepted : 16 January 2021
                Categories
                Subject: Original Article
                Subject: Psychiatric/Psychology

                Keywords: autism spectrum disorder,meta-analysis,small for gestational age
                Data availability:
                Keywords: autism spectrum disorder, meta-analysis, small for gestational age

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